Examining Clinical Features and Severe Neurologic Disease of Parechovirus Infection in Young Infants: A Multi-State Cohort Study.

BACKGROUND: Human parechovirus (HPeV) infection can result in severe disease in infants, including sepsis, seizures, brain injury, and death. In 2022, a resurgence of HPeV was noted in young infants. Spectrum of illness and outcomes remain to be fully described. METHODS: A multi-state retrospective cohort study was conducted to evaluate hospitalizations and outcomes of infants aged ≤6 months admitted in 2022 with laboratory-confirmed HPeV infection. Infants with severe disease were defined as having clinical seizures, or abnormalities on MRI or EEG during admission. Infants with severe vs non-severe disease were compared using descriptive statistics. RESULTS: 124 U.S. infants were identified with HPeV in 11 states. Cases of HPeV peaked in May and presented at a median of 25.8 days of life (0-194 d) with fever, fussiness, and poor feeding. Bacterial and other viral co-infections were rare. 33 (27%) of infants had severe neurologic disease, were more likely to present at an earlier age (13.9 vs 30 days of life, p<0.01), have preterm gestation (12% vs. 1%, p = 0.02), and present with respiratory symptoms (26% vs. 8%, p = 0.01) or apnea (41% vs. 1%, p <0.001). Subcortical white matter cytoxic cerebral edema was common in severe cases. Two infants with HPeV died during admission with severe neurologic HPeV disease; no infant with mild HPeV disease died. CONCLUSIONS: This is the largest, geographically-diverse U.S. study to describe the 2022 HPeV outbreak among infants. Longitudinal follow up of infants is needed to define predictors and outcomes of severe HPeV disease.

An unexpected COVID-19 diagnosis during emergency surgery in a neonate.

A 4-day-old, 3.3 kg infant presented with suspected intestinal malrotation, necessitating emergent diagnostic laparoscopy. Intra-operatively, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) came back positive. This is the first case report of emergency surgery and anesthesia in a positive SARS-CoV-2 newborn. This report highlights a neonate with an incidental positive SARS-CoV-2 test, no known exposure history, negative polymerase chain reaction maternal testing, and absence of respiratory symptoms who required modified pressure control ventilation settings to adequately ventilate with the high-efficiency particulate air filter in situ.

Connecting the Dots From Fever of Unknown Origin to Myelodysplastic Syndrome: GATA2 Haploinsufficiency.

Leukemia-predisposing conditions, such as GATA2 haploinsufficiency, are known for their high penetrance and expressivity profiles. These disorders pose a difficult diagnostic challenge to even the most experienced clinician when they first present. We describe the case of a 17-year-old male presenting with features of nontuberculous mycobacterial infection, pulmonary fibrinoid granulomatous vasculitis, and myelodysplasia in the setting of a pathogenic GATA2 frameshift mutation confirmed by next-generation sequencing. The broad differential for GATA2 haploinsufficiency requires prompt recognition of key clinical features and laboratory abnormalities towards directing diagnosis and guiding appropriate and perhaps life-saving therapy.

A Moraxella catarrhalis two-component signal transduction system necessary for growth in liquid media affects production of two lysozyme inhibitors.

There are a paucity of data concerning gene products that could contribute to the ability of Moraxella catarrhalis to colonize the human nasopharynx. Inactivation of a gene (mesR) encoding a predicted response regulator of a two-component signal transduction system in M. catarrhalis yielded a mutant unable to grow in liquid media. This mesR mutant also exhibited increased sensitivity to certain stressors, including polymyxin B, SDS, and hydrogen peroxide. Inactivation of the gene (mesS) encoding the predicted cognate sensor (histidine) kinase yielded a mutant with the same inability to grow in liquid media as the mesR mutant. DNA microarray and real-time reverse transcriptase PCR analyses indicated that several genes previously shown to be involved in the ability of M. catarrhalis to persist in the chinchilla nasopharynx were upregulated in the mesR mutant. Two other open reading frames upregulated in the mesR mutant were shown to encode small proteins (LipA and LipB) that had amino acid sequence homology to bacterial adhesins and structural homology to bacterial lysozyme inhibitors. Inactivation of both lipA and lipB did not affect the ability of M. catarrhalis O35E to attach to a human bronchial epithelial cell line in vitro. Purified recombinant LipA and LipB fusion proteins were each shown to inhibit human lysozyme activity in vitro and in saliva. A lipA lipB deletion mutant was more sensitive than the wild-type parent strain to killing by human lysozyme in the presence of human apolactoferrin. This is the first report of the production of lysozyme inhibitors by M. catarrhalis.

Identification of an outer membrane lipoprotein involved in nasopharyngeal colonization by Moraxella catarrhalis in an animal model.

Colonization of the human nasopharynx by Moraxella catarrhalis is presumed to involve attachment of this bacterium to the mucosa. DNA microarray analysis was used to determine whether attachment of M. catarrhalis to human bronchial epithelial (HBE) cells in vitro affected gene expression in this bacterium. Attachment affected expression of at least 454 different genes, with 163 being upregulated and 291 being downregulated. Among the upregulated genes was one (ORF113) previously annotated as encoding a protein with some similarity to outer membrane protein A (OmpA). The protein encoded by ORF113 was predicted to have a signal peptidase II cleavage site, and globomycin inhibition experiments confirmed that this protein was indeed a lipoprotein. The ORF113 protein also contained a predicted peptidoglycan-binding domain in its C-terminal half. The use of mutant and recombinant M. catarrhalis strains confirmed that the ORF113 protein was present in outer membrane preparations, and this protein was also shown to be at least partially exposed on the bacterial cell surface. A mutant unable to produce the ORF113 protein showed little or no change in its growth rate in vitro, in its ability to attach to HBE cells in vitro, or in its autoagglutination characteristics, but it did exhibit a reduced ability to survive in the chinchilla nasopharynx. This is the first report of a lipoprotein essential to the ability of M. catarrhalis to persist in an animal model.

Development of a LacZ-based transcriptional reporter system for use with Moraxella catarrhalis.

The lack of a transcriptional reporter system for use in Moraxella catarrhalis has hindered studies of gene regulation in this pathogen. PCR and recombinant DNA methods were used to insert a multicloning site (MCS) and promoterless full-length Escherichia coli lacZ gene, flanked by transcriptional terminators both immediately upstream and downstream, into the M. catarrhalis recombinant plasmid pWW115. Insertion into the MCS in the newly constructed plasmid pASE222 of M. catarrhalis promoter regions controlled by either a repressor (i.e., NsrR) or activator (i.e., PhoB) yielded transcriptional fusion constructs that were appropriately responsive to signal inputs dependent on the host strain genotype, as measured quantitatively by means of a Miller ß-galactosidase assay. The transcriptional reporter plasmid pASE222 should prove to be a useful tool for rapid screening of factors affecting gene expression in M. catarrhalis.

Missed Opportunity Encounters for Early Diagnosis of HIV Infection in Adolescents.

BACKGROUND: Early diagnosis of HIV infection improves patient outcomes and reduces transmission. Adolescents make up one-fifth of new HIV diagnoses in the United States. We sought to quantify the number of missed opportunity encounters (MOEs) before HIV diagnosis for adolescents at a pediatric hospital (PediHosp) and a proximate adult hospital which employs universal HIV screening in its emergency department (ED) (CountyHosp). METHODS: An observational study at 2 academic tertiary care hospitals in the United States that included all adolescents 13-20 years old with a new diagnosis of behaviorally-acquired HIV infection from 2006 to 2017. MOE were defined as any encounter at PediHosp or CountyHosp after the latter of the individual's 13th birthday or the date 3 months after the individual's most recent negative HIV screen, and before the encounter of HIV diagnosis. Comparisons were made by site of diagnosis and location of MOE. RESULTS: Two-hundred five subjects met inclusion criteria: 68% male, 76% Black and 81% men who have sex with men. There were 264 MOE, the proportion of adolescent ED encounters that were MOE at the PediHosp ED was 8.3 MOE per 10,000 encounters and the proportion at the CountyHosp ED was 1.2 (relative risk = 6.7; 95% CI: 4.1-11.0; P < 0.001). CONCLUSIONS: MOE for HIV diagnosis in adolescents occur frequently and are greater in number at a PediHosp as compared with a similar adult setting with universal screening. Universal HIV screening protocols at PediHosp may identify HIV-positive adolescents earlier.

Intrauterine Transmission of SARS-COV-2 Infection in a Preterm Infant.

We present a preterm infant who developed a fever and mild respiratory disease on the second day of life. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nasopharyngeal testing was positive at 24 and 48 hours of life. Placenta histopathology revealed SARS-CoV-2 infection by electron microscopy and immunohistochemistry. Further understanding of the risk factors that lead to in utero transmission of SARS-CoV-2 infection is needed.